In the course of myotube formation, myoblasts, which have divided from myogenic cells originating in undifferentiated mesodermal cells and grown to differentiate, will start synthesizing muscle-specific substances such as myosin and actin after its final division, and will lose cell boundaries at the fusion surface to be transformed into multinucleate syncytium named myotube through adhesion and fusion of cytoplasmic membranes with neighbouring cells of the same kind.
There have been already reported several kinds of membrane proteins involved in the myotube formation, such as N-Cadherin (Knudsen, K. A. et al., Expl. Cell Res., 188, 175-184 (1990), Merge, R. M. et al., J. Cell Sci., 103, 897-906 (1992)), M-Cadherin (Donalies, M. et al., Proc. Natl. Acad. Sci., U.S.A. 88, 8024-8028 (1991)), N-CAMs (Merge, R. M. et al., J. Cell Sci., 103, 897-906 (1992) and others), V-CAMs and Integrins (Rosen, G. D. et al., Cell 69, 1107-1119 (1992) and others).
However, the molecular mechanism has not yet been sufficiently understood concerning the course of formation of the multinucleate syncytium named myotube through adhesion and fusion of the cytoplasmic membranes of the myoblasts with each other.
On the other hand, the substances named “fusion peptides” have been known as an adhesion factor involved in the course of infection of cells with viruses (Morrison, T. G. Virus Res., 10, 113-136 (1988) and the others). Fertilin, which was recently isolated as a factor involved in sperm-egg adhesion, has been found to contain a sequence similar to the fusion peptide of rubella virus (Blobel, C. P. et al., Nature 356, 248-252 (1992) and the others).
Many substances having adhesion activity are known as mentioned above, and substances which may inhibit the activity of Integrins and the like have been developed and studied as potential medical agents.
The present inventors have now isolated novel substances involved in adhesion. Particularly, on the assumption that some fusion peptide-like adhesion factor like in sperm-egg adhesion may be involved in adhesion and fusion of the myoblasts with each other in the course of myotube formation, the novel substances involved in cell adhesion have been cloned and named “Meltrins”, by using highly conserved sequences in Fertilin α and β as a probe.